Articular cartilage damage is a major cause of disability in the form of arthritis and joint trauma. Because articular cartilage lacks the ability to effectively repair itself, articular cartilage repair is an unsolved clinical problem.
Growth factors, such as insulin-like growth factor-I (IGF-1), promote articular chondrocyte reparative activity. When delivered to articular cartilage as potential therapeutic agents, these factors are limited by rapid elimination from the joint, slower uptake by the articular cartilage containing the target cells, and, when present in the cartilage or repair tissue, are subject to diffusion out of the tissue where it is needed.
Biologic agents are needed that can promote cartilage biosynthesis in vitro and in vivo. A promising candidate for improving articular chondrocyte function is IGF-1. This polypeptide growth factor has been shown to stimulate the synthesis of type-2 collagen and aggrecan, two principle constituents of cartilage matrix, to stimulate the division of articular chondrocytes and to decrease the endogenous catabolic activity of these cells. Therapeutic application of IGF-1 to cartilage repair has been reported in animal models when delivered as a protein, or by gene transfer. However, an unpublished clinical trial of IGF-1 delivery to human knee joints was evidently unsuccessful. A major limitation of current approaches to IGF-1 therapy include: 1) The rapid removal of IGF-1 from the joint through the synovium, 2) the relatively slow diffusion of IGF-1 into the articular cartilage where it can act on the cells, and 3) limited responsiveness of arthritic chondrocytes to the IGF-1. A means of simultaneously providing cells, IGF-1, and of gradual IGF-1 release over time is needed.
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